Method for simplified shipping of clinical specimens and optional direct analysis

ABSTRACT

A method for shipping clinical specimens lawfully, safely, cheaply, and easily without regard to some or all of the laws, rules, and regulations regarding samples that may contain infectious and/or etiologic agents. Optional method of direct analysis of shipped samples.

BACKGROUND OF THE INVENTION

[0001] 1. Field of the Invention

[0002] The present invention relates to a method for the simplifiedshipping of clinical specimens, especially specimens that may contain anetiologic agent. The present invention further relates to the laboratoryanalysis of the shipped specimen, preferably directly upon receipt andwithout further substantial sample preparation.

[0003] 2. Background of the Invention

[0004] The laboratory analysis of human or animal material, including,but not limited, to excreta, secreta, blood and its components, tissue,and tissue fluids is a necessity of modern medicine for the purposes ofdiagnosis. Most if not all Americans are familiar with “blood tests”used to determine their cholesterol level, the presence or absence ofvarious microorganisms, and, depending upon level of sophistication,phenotyping, genotyping, etc. Such analysis is also used in therapeuticdrug monitoring (TDM), which determines the quantity of a drug in theblood. TDM is now routine for approximately 20 different drugs for whichdosing level is an issue and for which immunochemical assays have beencommercialized. TDM is extremely important for individualized therapy,and it is a tool used to avoid both toxic and sub-therapeutic bloodconcentrations (and the drug resistance that sub-therapeutic levels caninduce in, for example, the treatment of infectious diseases).

[0005] One problem encountered in the laboratory analysis of clinicalspecimens is that oftentimes the laboratory where analysis is conductedis located apart from where samples are collected. Thus, the clinicalspecimen must somehow be transported to the site of the laboratory. Thetransportation of a clinical and, especially, an infectious specimen ishighly regulated, complicated and expensive because of safety issues,health concerns, Department of Transportation regulations, and variousother laws, rules, and regulations of the States and the United States,and foreign countries. In fact, the packaging and shipping standards forinfectious substances in the United States are higher than those for anyother class of dangerous goods except high-activity radioactivematerials.

[0006] For example, Title 49 of the Code of Federal Regulations (CFR)governs the shipping of hazardous materials, and essentially encompassesthe International Air Transport Association regulations regardingdangerous materials shipping, including the shipment of infectioussubstances that can affect a human. 49 CFR 171.8, 172.101, and 173.134,as well as 42 CFR, particularly sections 72.1-72.5, all incorporatedherein by reference (current as of the filing date of this application),govern the shipment of etiologic agents (a viable microorganism or itstoxin that causes, or may cause, human disease). As noted in 42 CFR72.2, it is unlawful to knowingly transport or cause to be transportedspecimens and products that one reasonably believes may contain anetiologic agent unless certain packaging standards and requirements aremet. Under 42 CFR 72.3, an extensive, non-comprehensive list of suchetiologic agents is provided (incorporated herein by reference), andstrict packing requirements, etc. are specified, as is a particularlabel that must be placed on the outer shipping containers of allmaterials containing etiologic agents. Of course, any package thatpossesses special labeling commands a significant surcharge that ispayable to the shipping company. What is more, the special packagingthat is required has become an industry in and of itself, and it is nowcommon to spend at least $39 to purchase a box for a single sample (see,for example, part numbers STP100, STP300, and STP370, all found atwww.cargopak.com/saftpak.htm and at www.saftpak.com). Even when ashipper does not reasonably believe that a clinical specimen contains anetiologic agent, readying such a sample for transport remainsburdensome, expensive, and requires staffing by individuals who arefully apprised of all shipping regulations and who possess documentationof ongoing participation in training programs.

[0007] Another problem caused by the transport or shipping of clinicalspecimens to a laboratory for analysis is the integrity of the samplebeing shipped. If the sample is not maintained at a proper temperatureduring transport it is possible that the sample when analyzed isdifferent from that when it was obtained, and that the results providedby the laboratory do not reflect the true state of the patientscondition. The incorporation of dry ice or cold packs in a packageincreases the weight and, hence the shipping cost. The convenience andtimeliness of shipping temperature-controlled packages is low as well,since most receiving laboratories state that shipments should be madefrom Mondays to Thursdays only. What's more, because carbon dioxide istoxic, the transport of dry ice by aircraft adds significant regulatoryburden.

[0008] The inventor knows of three organizations that openly promote thefee-for-service measurement of antiviral drug concentrations in bodyfluids of HIV-infected individuals. Specifically, these organizationsare University of Liverpool, National Jewish Medical and ResearchCenter, and Specialty Laboratories. In each case, the support literaturefrom these organizations ask that untreated, known infectious plasma orserum be shipped, in a legally proper manner, to the analysis facility.Hence, the burden of precise compliance to all shipping regulationsregarding etiologic agents, dry ice, etc. rests squarely on the shipper.Further, the real cost of sample analysis is inflated because of thepackaging material costs, shipping surcharges, staffing byhighly-trained shipping specialists, etc.

[0009] The practical result of the difficulties encountered in shippinga clinical specimen to a laboratory for analysis (i.e., shippingrequirements, increased cost, maintenance of sample integrity, etc.) isillustrated by the website for Specialty Laboratories(www.specialtylabs.com), a research-based clinical reference laboratorythat provides diagnostic, prognostic, and monitoring services. On thiswebsite under “Domestic & International Shipping Procedures” it isexplained that the shipper of medical specimens is required to complywith the rules and guidelines for transport of such materials, and theshipper is ultimately responsible for all decisions that are maderegarding packaging. Information is provided that outlines, with anintermediate level of detail, the various steps the shipper must gothrough in preparing a clinical specimen for shipment. Investigationinto the shipment of such samples through overnight courier services,such as FedEx, has revealed that, beyond the normal fees based on weightand destination, substantially higher charges are incurred for sampleslabeled in accordance with the laws, rules and regulations that governthe shipping of clinical specimens that may contain etiologic agents.

OBJECTS OF THE INVENTION

[0010] It is one object of the invention to provide a method for thelawful shipment of clinical specimens that does not require compliancewith U.S. laws, rules and regulations (including those of the States)regarding the shipment of samples or material that may contain anetiologic agent. (For applications in countries other than the U.S. thelaws, rules and regulation are those of the examining country. Allcountries of the world are included such as Japan, the countries ofEurope, South America, etc.)

[0011] It is a further object of the invention to provide a samplecontainer useful for shipment of samples or material without thenecessity of following the various laws, rules, and regulationsregarding the shipment of etiologic materials.

[0012] It is a further object of the invention to provide methodinstructions and/or equipment to allow for the inactivation of clinicaland etiologic specimens and their conversion from etiologic tonon-etiologic or from biohazardous to non-biohazardous, the methodequipment including a sample container for the shipment of theinactivated, non-etiologic sample in accordance with the inventionmethod for shipment.

[0013] It is a further object of the invention to provide for theshipping of clinical specimens at ambient temperatures.

[0014] It is another object of the present invention to provide aprocess wherein biological, clinical, etc. samples that may be etiologicin nature are inactivated and made non-etiologic prior to shipping,lawfully shipped without compliance with at least one of the variouslaws, rules, and regulations regarding the shipping of etiologicmaterials, optionally received at an analysis laboratory, and optionallyanalyzed at said laboratory for example directly upon receipt andwithout further significant sample preparation.

[0015] These and other objects will become apparent as the invention ismore thoroughly explained in the following detailed description.

DETAILED DESCRIPTION

[0016] In one embodiment the present invention relates to the shipmentof a sample or material (hereinafter referred to as a clinical specimen)anywhere, including in interstate, intrastate, or internationalcommerce. By “clinical specimen” the inventor means any human or animalmaterial including, but not limited to, excreta, secreta, blood and itscomponents, tissue, tissue fluids, and biological products that may ordo contain an infectious or etiologic agent, excluding explanted medicaldevices and tissue, fluid, etc. adhering to an explanted medical device.A particularly preferred type of clinical specimen according to theinvention is one that does contain an infectious or etiologic agent,where the term “etiologic agent” is defined herein as any microorganismor its toxin that causes, or may cause, human disease. The term“shipment” as used herein means physical transport to a directedlocation, whether effected by mail, courier, vehicle, ship, airplane,etc. and includes all common forms of shipment well known to those ofordinary skill in the art such as the national mail system, commercialcourier services such as FedEx, Airborne, Emery Worldwide, DHL, etc.,UPS, trucking services, car delivery services, bicycle couriers,pedestrian foot delivery services, etc. “Shipping” and “shipped” meansthe act of placing the thing to be physically transported in the handsof, the custody of, etc., a shipper such as the U.S. mail system,commercial courier services such as FedEx, Airborne, Emery Worldwide,DHL, etc., UPS, trucking services, car delivery services, bicyclecouriers, pedestrian foot delivery services, etc. with deliveryinstructions and the subsequent shipment of the thing as received by theshipper. Excluded from the term “shipment” is the movement of the thingwithin a building or within a campus, or within a complex of associatedbuildings. Excluded from the term “shipping” is the act of placing thething to be physically transported in the hands of, custody of, etc. ashipper with delivery instructions limited to delivery within a buildingor within a campus, or within a complex of associated buildings. In apreferred embodiment, the clinical specimen is shipped to (transportedto) a testing laboratory for the purpose of being subjected to a testoffered by the laboratory. For examples of tests useful herein,Specialty Laboratories, mentioned above, lists hundreds of such tests atwww.specialtylabs.com under the heading of “test menu”, all of which arehereby incorporated by reference. Examples include amikacin (test#4900), epinephrine (test #3270), phenobarbital (test #4142), zidovudine(test #4959), etc. Another listing of tests useful herein is the MayoMedical Laboratories 2000 Test Catalog, 1999, Mayo Press, Rochester,Minn., incorporated herein by reference.

[0017] In a highly preferred embodiment, the clinical specimen issubjected to pre-shipping treatment that renders the clinical specimennon-infectious and non-etiologic (i.e., converts the clinical specimento a “safe clinical sample”) and that optionally also provides a samplethat may be, and that preferably later is, capable of being directlysubjected to the intended laboratory test without further significantsample pre-treatment.

[0018] Thus, a preferred embodiment of the present invention is a methodfor the shipping of clinical specimens lawfully without compliance withat least one of the various State, U.S., and, for countries other thanthe U.S., foreign national, as well as any applicable international,laws, rules, and regulations regarding shipment of materials that maycontain etiologic agents, thereby avoiding the increased costsassociated with shipping according to such laws, rules, and regulationsand providing a safer, simpler, cost-effective method for the shipmentof such samples. In a further preferred embodiment, the method includesreceipt of the shipped clinical specimen (i.e., the safe clinicalsample) by a laboratory, and in a highly preferred embodiment furtherincludes the direct laboratory analysis of the sample as received (orafter minimal preparation such as centrifugation, concentration,evaporation, and/or filtration). With the method of the presentinvention it is envisioned that the remote laboratory testing of aclinical specimen that has been converted into a safe clinical samplecan be accomplished quickly (for example, within one day or less) andmore cheaply than is the current state of the art with greatefficiencies being realized in both the safer, simpler, easier, andcheaper method of shipping and, if laboratory testing is included in themethod, with the cheaper and easier testing of the sample by eitherdirect injection into the testing apparatus or direct subjection to theanalysis method (or injection or subjection after minimal preparationsuch as centrifugation, concentration, evaporation, and /or filtration).It is envisioned that, with respect to TDM, the present method modelwill become a benchmark, allowing for relatively inexpensive, accurate,reproducible overnight turnaround for standard and even esotericlaboratory test results, thereby increasing the effectiveness of medicaltreatment and avoiding problems associated with sub-optimal therapy.

[0019] A preferred present invention method for converting a clinicalspecimen into a safe clinical sample, thereby converting the clinicalspecimen from a very expensive and somewhat complicated sample to shipinto a very simple, safe, easy, cheap sample to ship, is treatment ofthe clinical specimen with enough water-miscible organic solvent torender the specimen non-etiologic and non-infectious (e.g., contact,mixing, etc.). Those of ordinary skill in this art know how to determineif a sample may contain an etiologic or infectious agent, and they knowhow to determine whether a sample has been rendered non-infectious andnon-etiologic. In a highly preferred embodiment, alchohol (preferablyreagent ethanol, pure ethanol, reagent alcohol, or denatured alcohol) ismixed with the specimen to provide preferably at least 70% by volumealcohol. As an example, in order to prepare a noninfectious,non-etiologic safe clinical sample for shipping according to the presentinvention, a particular volume (for example 1.00 ml) of a body fluidsuch as urine, plasma, cerebral spinal fluid, whole blood, serum, etc.is mixed with sufficient alcohol to provide a 70 vol. % alcoholsolution. Of course, higher and lower amounts of alcohol can be utilized(such as 10, 20, 30, 40, 50, 60, 70, 80, 90, 95 and higher vol. %), butpreferably 70 vol. % and above are used. In determining the amount ofalcohol to add, one can assume that clinical specimens consisting ofbodily fluids are essentially water. Thus, in the example above, 2.33 mlof anhydrous reagent alcohol would be added to the 1.00 ml of bodilyfluid to provide at least a 70 vol. % alcohol solution. Of course, moreor less alcohol could be added, if desired. In this way, methodinstructions and equipment may be provided that allows one to render aclinical specimen that may or does contain an etiologic and/orinfectious agent non-infectious and non-etiologic and also, importantly,allow for lawful shipment of e.g., the safe clinical sample withoutcompliance with at least one of the various laws, rules, and regulationsregarding the shipment of specimens that may contain infectious oretiologic agents. If denatured alcohol is the solvent of choice, such asafe clinical sample may be subject to certain other rules andregulations regarding, for example, flammable samples, but the samplewould not be subject to the significant and costly rules and regulationsregarding shipment of, e.g., etiologic agents.

[0020] In addition to alcohol, other water-miscible organic solvents maybe used for the invention purpose described above, includingacetonitrile, methanol, and 2-propanol, among others. In a highlypreferred embodiment, the solvent used does not affect the clinicalspecimen in a way that would affect the laboratory testing procedureintended for the specimen. It is particularly noteworthy that theinvention method allows the user to avoid, if desired, the use of morehazardous and reactive chemicals that are often used for inactivation ofetiologic agents, including chemicals such as formaldehyde, formalin,paraformaldehyde, glutaraldehyde, peroxygen-based compounds, andhalogen-releasing compounds.

[0021] Another preferred present invention method for converting aclinical specimen into a safe clinical sample, thereby converting theclinical specimen from a very expensive and somewhat complicated sampleto ship into a very simple, safe, easy, cheap sample to ship, is passageof the clinical specimen through a sterilizing filter to render thespecimen non-etiologic and non-infectious. In a highly preferredembodiment, the clinical specimen is passed through a sterilizing filterthat possesses pores preferably no greater than 0.2 microns in size. Asan example, in order to prepare a non-infectious, non-etiologic safeclinical sample for shipping according to the present invention, aparticular volume (for example 1.00 ml) of a body fluid such as urine,plasma, cerebral spinal fluid, whole blood, serum, etc. is passedthrough a 0.2 micron sterilizing filter. Of course, larger and smallerpore sizes can be utilized (such as 1.0 micron, 0.8 micron, 0.6 micron,0.4 micron, 0.3 micron, 0.1 micron, 0.05 micron, 0.005 micron, andlower), but preferably 0.2 micron and smaller are used. In this way,method instructions and equipment may be provided that allows one torender a clinical specimen that may or does contain an etiologic and/orinfectious agent non-infectious and non-etiologic and also, importantly,allow for lawful shipment of e.g., the safe clinical sample withoutregard to at least one of the various laws, rules, and regulationsregarding the shipment of specimens that may contain infectious oretiologic agents.

[0022] Of course, the conversion methods noted above (filtration andsolvent treatment) may be used in combination sequentially in any orderor used together (e.g., the clinical specimen diluted with alcohol ispassed through a filter).

[0023] Heat treatment of blood-derived samples at 56° C. can inactivatethe HIV virus, for example. A heat treatment period ranging from 0.5hours to as much as 5 hours (Resnick, et al., JAMA (1986) 255, 1887-91)is recommended, however, and even the shortest 0.5 hour exposure canmodify free drug concentrations (Dasgupta, et al., Ther. Drug Monit.(1999) 21, 421-5). Such conditions are too harsh for labile molecules,as hydrolysis and other unwanted reactions will occur. Although heatingof known infectious plasma, serum, etc. prior to or after mixing withwater-miscible organic solvents and/or filter sterilization is laborintensive and unnecessary, the combination of these steps is includedherein.

[0024] Also included herein, alone or in any combination with theconversion techniques described above, is the inactivation of theclinical specimen with any other agent or treatment prior to shipping.Such agents include INACTINE® products and those described in U.S. Pat.No. 5,891,705, incorporated herein by reference.

[0025] An important benefit of the present invention method forrendering a clinical specimen safe (i.e., non-infectious andnon-etiologic), in addition to the lessened costs and requirementsregarding lawful shipping, is that the sample, once rendered safeaccording to the present invention method (by solvent addition, filtersterilization, use of some other agent, heating, etc.), may be shippedwithout temperature control, meaning that traditional cooling with dryice, etc. is not required when shipping the invention safe clinicalsample. In this regard, dual savings are realized—the high cost anddanger of shipping unsafe samples is avoided as is the high cost,regulatory burden, and difficulty of shipping samples that must be keptcold, for example with dry ice. Of course, temperature control may beused if desired, such as dry ice, ice packs, etc., and this is preferredfor labile analytes.

[0026] In this sense, the present invention method of clinical specimentreatment (for example with a water-miscible organic solvent) so as torender the specimen safe followed by simple shipping lawfully withoutcompliance with at least one of the various laws, rules and regulationsregarding the shipment of, e.g., etiologic samples provides a new anduseful method for shipping as well as a new and useful method that cancapitalize on economies not previously recognized or utilized. In thisway, the simple steps of adding, for example, alcohol to a clinicalspecimen, or filter sterilization, or a combination thereof, to renderit safe followed by lawfully shipping the treated sample without regardto the laws, rules, and regulations that govern the shipment of, e.g.,clinical specimens that may contain etiologic agents, provide asignificant advance in the art not previously recognized. While it haspreviously been recognized that 70 vol. % denatured alcohol, heat, etc.can be used to inactivate etiologic agents and that filter sterilizationcan remove etiologic agents, it has not previously been recognized thatif clinical specimens are so rendered prior to shipping they may then beshipped simply, lawfully, safely, cheaply, and easily without regard tothe laws, rules, and regulations regarding shipment of etiologicspecimens, and/or without regard to the maintenance of a certaintemperature or general temperature control, such as cooling with dryice, etc.

[0027] The “hardware” utilized in accomplishing what will be termed the“sample inactivation/shipping” aspect of the present invention describedabove is not particularly limited. Practical considerations preferablyinclude containment of the sample in a closed, preferably non-leakingcontainer that is not damaged or leached by the water-miscible solvent.With regard to packaging for shipping, practical considerations shouldbe borne in mind in view of the realities encountered by the variouscommercial and governmental shipping concerns. While no specialaccommodations are required, it is preferred that shipping occur in anenvelope, box, etc. that will survive intact its transport to theultimate destination.

[0028] Several sample collection containers and assemblies are known inthe art, and all may be used herein. Examples include GB1, 542,411, U.S.Pat. Nos. 1,594,370, 3,163,160, 3,915,806, 4,336,880, 4,311,792,4,604,360, 4,732,850, 4,788,985, 4,813,432, 5,313,959, 5,266,266,5,425,915, 5,658,531, 5,710,041, 5,726,062, 5,786,227, 5,786,228,5,859,374, 5,879,635, 4,211,323, 4,150,950 and 5,511,558, allincorporated herein by reference. One particularly preferred embodimentfor use in the sample inactivation/shipping embodiment of the presentinvention is a container that itself contains an inner container. Theinner container holds the water-miscible solvent of the invention, forexample, reagent alcohol. The volume of solvent held in the innercontainer (e.g., a frangible ampoule) may be pre-measured in accordancewith the amount of clinical specimen that is directed to be placed inthe container. In using this arrangement the clinical specimen is placedin the container, the container is optionally closed, and the innercontainer is manipulated such that the water-miscible organic solventmixes with, contacts, etc. the clinical specimen such that it isrendered non-infectious and non-etiologic. If desired, this solutioncould then be passed through a sterilizing filter assembly. As notedabove, it is preferred that the final volume percent of water-miscibleorganic solvent is at least 70%, including 75, 80, 85, 90 and greaterthan 90% by volume, and that the filter pores are less than 0.2 micron,including 0.1 micron, 0.05 micron, and 0.005 micron. Ethanol contentsthat are 70-75% by volume show excellent performance in HIV-inactivationassessments (van Bueren et al., J. Hosp. Infection (1994) 28, 137-148;Druce et al., J. Hosp. Infection (1995) 30, 167-180; both incorporatedherein by reference). Filters with pore sizes of 0.2 micron and smallerare used to sterilize medicines, fluids, and blood-derived products thatare meant for intravenous, intramuscular, etc. use (Brown et al., Dev.Biol. Stand., “Viral Safety and Evaluation of Viral Clearance fromBiopharmaceutical Products.” (1996) 88, 319-326; McKinnon et al., Am. J.Hosp. Pharm. (1993) 50, 1921-1936; Anonymous, PDA J. Pharm. Sci.Technol., “Parenteral Drug Association Technical Report No. 26,Sterilizing Filtration of Liquids.” (1998) 52 (No. 3, Supplement), 1-31;all incorporated herein by reference). It is preferred that thecontainer can be sealed such that it need only be placed in ahigh-quality plastic bag containing absorbent prior to placement in anenvelope, box, etc. to be shipped and thus configured such that it canwithstand such shipping without breakage, leakage, etc. Thus, and inaccordance with the present invention, method equipment may include oneor any combination of a clinical specimen container, a shippingcontainer, method instructions, etc. The shipping container may bepre-addressed and is preferably configured such that the specimencontainer may be shipped therein. Optionally present in the methodequipment, optionally located in the specimen container, is a certainvolume of water-miscible organic solvent or instructions regarding theuse of water-miscible organic solvents optionally with method equipmentcomponents. Also optionally present in the method equipment, optionallyattached to the specimen container, is a sterilizing filter assemblyand/or instructions regarding the use of a sterilizing filter assemblywith other, e.g., method equipment components. The water-miscibleorganic solvent is preferably provided such that it can be contactedwith the clinical specimen, sealed within the specimen container, andthe specimen container shipped in the shipping container, for example toa testing laboratory, lawfully without regard to the various laws,rules, and regulations regarding the shipment of, e.g., etiologic agentsand optionally without temperature controls such as packing on dry ice,etc. In a preferred embodiment, the water-miscible organic solventitself, or the method equipment (or, if the method equipment does notcontain solvent, the instructions regarding the solvent) may contain aninternal standard (or instructions concerning the use of an internalstandard) that allows a testing laboratory to quantitatively determinethe amount of whatever is being tested for in the specimen.

[0029] Another embodiment of the present invention relates to theanalysis of safe clinical samples, made safe (e.g., converted) accordingto the invention. In this further embodiment, a safe clinical sample issimply directly analyzed with minimal or no sample pre-treatment. Forexample, a clinical specimen that has been diluted to 70 vol. % reagentalcohol may be directly analyzed on an LC system or an LC-MS system, oranalyzed after centrifugation, concentration, evaporation, and/orfiltering. The system of analysis could not be more simple: the safeclinical sample containing, e.g., 70% by volume reagent alcohol, issimply directly (or after centrifugation, concentration, evaporation,and/or filtering) injected into a laboratory instrument for analysis orsubjected to the desired laboratory test. If one wishes to preserve theperformance of the instrument, protective measures known in the art suchas a in-line filter, a guard column, or a column-switching valve, etc.may be taken. Lab tests that do not depend upon specimen-associatedenzyme activity and whose target (analyte) being tested for does notprecipitate due to water-miscible organic solvent treatment, arepreferred. Lab tests whose target (analyte) being tested for does passthrough a sterilizing filter assembly are preferred. If an internalstandard is not added to the clinical specimen at the point of origin orpoint of shipping, it may be added at the recipient laboratory prior toanalysis. While it is known that some laboratories use water-miscibleorganic solvents, concentrated acids, and metal salts to precipitateproteins from samples prior to analysis, it is believed that 1)acetonitrile is used in the vast majority of cases and that 2) thesemethods have been used on an in-house basis only, and not on clinicalspecimens prior to shipping.

[0030] In a highly preferred embodiment, a further method is providedthat combines the sample inactivation/shipping embodiment describedabove in combination with the direct analysis of the sample upon receiptat a laboratory. This model provides for highly effective and costefficient shipping due to the non-etiologic and non-infectious nature ofthe sample and the lack of a requirement for temperature control (dryice, etc.) while at the same time providing a sample that is “analysisready,” meaning that no further sample preparation is required prior tolaboratory testing. In this way, a method is described that providesextremely simple and quick turnaround of laboratory test results forclinical specimens.

EXAMPLE

[0031] The following example contemplates obtaining (receiving) aclinical specimen at a location remote from the testing laboratory,converted into a safe clinical sample according to the invention, andshipping to the laboratory preferably without compliance with at leastone law, rule or regulation concerning the shipment of a material thatmay contain an etiologic or infectious agent.

[0032] After a package is received from the courier, etc., the sample isentered into the laboratory information management system by way ofbarcode scanning, etc. The accuracy of the inactivation (conversion)step, wherein the clinical specimen was, e.g., previously added to themethod equipment, can be assessed by weighing the safe clinical sample,by determining the ethanol:water ratio present in the sample, etc. Thesample is then either centrifuged, concentrated, evaporated, filtered,or not given any further treatment. The sample may then be injected (100μL, CTC Analytics, for example) directly into an HPLC system (Shimadzu,for example), then analytes and internal standard may be eluted from thecolumn (a 4.6 mm Keystone Betasil column, for example) using a gradientor a isocratic mobile phase system (water, acetonitrile, formic acid,for example). The analytes and internal standard may be detected andquantitated by a mass spectrometer (PE Sciex triple-quadrupole, forexample). The batch may then be approved by a medical technologist or aphysician, then each report is signed and transmitted to the requestingphysician.

[0033] Examples of preferred embodiments described herein, which thoseof ordinary skill in the art are now capable of understanding, makingand using in view of the present specification, include the following:

[0034] A. A method of shipping, comprising contacting a clinicalspecimen with sufficient water-miscible organic solvent to convert theclinical specimen into a safe clinical sample, and shipping said safeclinical sample.

[0035] B. A method of shipping, comprising passing a clinical specimenthrough a sterilizing filter assembly with sufficiently small pores toconvert the clinical specimen into a safe clinical sample, and shippingsaid safe clinical sample.

[0036] C. A method of shipping, comprising contacting a clinicalspecimen with sufficient water-miscible organic solvent and passingthrough a sterilizing filter assembly with sufficiently small pores toconvert the clinical specimen into a safe clinical sample, and shippingsaid safe clinical sample.

[0037] D. The method of A, B, and C, wherein said safe clinical sampleis shipped to a testing laboratory.

[0038] E. The method of A, B, C, and D, wherein said safe clinicalsample is lawfully packaged and labeled for shipping in a manner thatdoes not comply with at least one State or Federal law, rule, orregulation regarding the shipping of material which may contain aninfectious or etiologic agent. The regulations include Titles 42 and 49of the code of Federal Regulations, both incorporated herein byreference, and the IATA regulations, also incorporated herein byreference.

[0039] F. The method of A, B, C, D, and E, wherein said safe clinicalsample is packaged without any provision of sample temperature controlor maintenance.

[0040] G. The method of A, B, C, D, E, and F, wherein said safe clinicalsample is received by said laboratory and directly subjected tolaboratory analysis without substantial sample preparation.

[0041] H. The method of A, B, C, D, E, F, and G, wherein the laboratoryanalysis determines the amount or concentration of a chemical in thesample.

[0042] I. The method of A, B, C, D, E, F, G, and H, wherein thelaboratory analysis determines the amount or concentration of a drug inthe sample.

[0043] J. The method of A, B, C, D, E, F, G, H, and I, wherein saidwater-miscible organic solvent is ethanol.

[0044] K. The method of A, B, C, D, E, F, G, H, and I, wherein saidwater-miscible organic solvent is denatured alcohol.

[0045] L. The method of A, B, C, D, E, F, G, H, and I, wherein saidsterilizing filter assembly possesses pores of 0.2 microns or less.

[0046] M. The method of A, B, C, D, E, F, G, H, I, J, K and L, whereinsaid clinical specimen does contain an etiologic agent.

[0047] N. Equipment for effecting any method noted above.

[0048] O. The equipment of N, further containing invention methodinstructions.

[0049] P. The equipment of N and O, containing a shipping containerthat, when shipped, does not comply with at least one law, rule orregulation concerning the shipping of infectious or etiologic agents.

[0050] With regard to this invention being utilized in foreigncountries, and in any PCT or foreign application based upon thisapplication, it is to be understood that the various laws, rules, andregulations referenced above include those laws, rules and regulationsof all foreign countries, territories, possessions, etc. and eachforeign country, possession, territory, etc.

[0051] Obviously, numerous modifications and variations of the presentinvention are possible in light of the above teachings. It is thereforeto be understood that within the scope of the appended claims, theinvention may be practiced otherwise than as specifically describedherein.

1. A method of shipping, comprising converting a clinical specimen intoa safe clinical sample, and shipping said safe clinical sample.
 2. Themethod of claim 1, wherein said safe clinical sample is shipped to atesting laboratory.
 3. The method of claim 1, wherein said safe clinicalsample is lawfully packaged and labeled for shipping in a manner thatdoes not comply with at least one State or Federal law, rule, orregulation regarding the shipping of a clinical specimen.
 4. The methodof claim 2, wherein said safe clinical sample is lawfully packaged andlabeled for shipping in a manner that does not comply with at least oneState or Federal law, rule, or regulation regarding the shipping of aclinical specimen.
 5. The method of claim 1, wherein said safe clinicalsample is shipped without any provision for sample temperature controlor maintenance.
 6. The method of claim 2, wherein said safe clinicalsample is shipped without any provision for sample temperature controlor maintenance.
 7. The method of claim 4, wherein said safe clinicalsample is shipped without any provision for sample temperature controlor maintenance.
 8. The method of claim 2, wherein said safe clinicalsample is received by said laboratory and directly subjected tolaboratory analysis without substantial sample preparation.
 9. Themethod of claim 4, wherein said safe clinical sample is received by saidlaboratory and directly subjected to laboratory analysis withoutsubstantial sample preparation.
 10. The method of claim 6, wherein saidsafe clinical sample is received by said laboratory and directlysubjected to laboratory analysis without substantial sample preparation.11. The method of claim 8, wherein the laboratory analysis determinesthe amount or concentration of a drug in the sample.
 12. The method ofclaim 9, wherein the laboratory analysis determines the amount orconcentration of a drug in the sample.
 13. The method of claim 10,wherein the laboratory analysis determines the amount or concentrationof a drug in the sample.
 14. The method of claim 8, wherein thelaboratory analysis determines the amount or concentration of a chemicalin the sample.
 15. The method of claim 9, wherein the laboratoryanalysis determines the amount or concentration of a chemical in thesample.
 16. The method of claim 10, wherein the laboratory analysisdetermines the amount or concentration of a chemical in the sample. 17.The method of claim 1, wherein said water-miscible organic solvent isethanol or denatured alcohol.
 18. The method of claim 2, wherein saidwater-miscible organic solvent is ethanol or denatured alcohol.
 19. Themethod of claim 4, wherein said water-miscible organic solvent isethanol or denatured alcohol.
 20. The method of claim 5, wherein saidwater-miscible organic solvent is ethanol or denatured alcohol.
 21. Themethod of claim 8, wherein said water-miscible organic solvent isethanol or denatured alcohol.
 22. The method of claim 14, wherein saidwater-miscible organic solvent is ethanol or denatured alcohol.
 23. Themethod of claim 1, wherein said clinical specimen does contain anetiologic agent.
 24. The method of claim 2, wherein said clinicalspecimen does contain an etiologic agent.
 25. The method of claim 4,wherein said clinical specimen does contain an etiologic agent.
 26. Themethod of claim 5, wherein said clinical specimen does contain anetiologic agent.
 27. The method of claim 8, wherein said clinicalspecimen does contain an etiologic agent.